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Allergic Disease and Atopic Sensitizatin in Children Related to Farming and Anthroposophic Lifestyle—The PARSIFAL Study
Abstract
The prevalence of allergic diseases has increased rapidly in recent decades, particularly in children. For adequate prevention it is important not only to identify risk factors, but also possible protective factors. The aim of this study was to compare the prevalence of allergic diseases and sensitization between farm children, children in anthroposophic families, and reference children, with the aim to identify factors that may protect against allergic disease.
The study was of cross-sectional design and included 14,893 children, aged 5-13 years, from farm families, anthroposophic families (recruited from Steiner schools) and reference children in Austria, Germany, The Netherlands, Sweden and Switzerland. A detailed questionnaire was completed and allergen-specific IgE was measured in blood.
Growing up on a farm was found to have a protective effect against all outcomes studied, both self-reported, such as rhinoconjunctivitis, wheezing, atopic eczema and asthma and sensitization (allergen specific IgE > or = 0.35 kU/l). The adjusted odds ratio (OR) for current rhinoconjunctivitis symptoms was 0.50 (95% confidence interval (CI) 0.38-0.65) and for atopic sensitization 0.53 (95% CI 0.42-0.67) for the farm children compared to their references. The prevalence of allergic symptoms and sensitization was also lower among Steiner school children compared to reference children, but the difference was less pronounced and not as consistent between countries, adjusted OR for current rhinoconjunctivitis symptoms was 0.69 (95% CI 0.56-0.86) and for atopic sensitization 0.73 (95% CI 0.58-0.92).
This study indicates that growing up on a farm, and to a lesser extent leading an anthroposophic life style may confer protection from both sensitization and allergic diseases in childhood.
... This increase is probably linked to major societal and environmental changes, such as industrial development and air pollution (4). Moreover, lifestyles, living environments, and exposure to chemical hazards, such as pesticides, in early life seem related to allergic sensitization, eczema, and asthma later in life (5)(6)(7)(8)(9)(10). ...
... In the Norwegian Mother and Child Cohort Study (MoBa) study, frequent consumption of organic vegetables during pregnancy was associated with reduced risk of pre-eclampsia for the mother and hypospadias in offspring (12,13). Studies conducted in anthroposophic communities suggest that OF consumption may have a protective effect on allergies and atopy (5,6,10,11,14), even if distinguishing the role of OFs from that of other factors linked to anthroposophic lifestyles was difficult (5,10). ...
... In the Norwegian Mother and Child Cohort Study (MoBa) study, frequent consumption of organic vegetables during pregnancy was associated with reduced risk of pre-eclampsia for the mother and hypospadias in offspring (12,13). Studies conducted in anthroposophic communities suggest that OF consumption may have a protective effect on allergies and atopy (5,6,10,11,14), even if distinguishing the role of OFs from that of other factors linked to anthroposophic lifestyles was difficult (5,10). ...
Objectives: To assess (1) whether a history of allergy is associated with feeding with organic foods (OFs) during the complementary feeding period and (2) whether OF consumption in infancy is related to the incidence of respiratory and allergic diseases up to age 5.5 years.
Study Design: Analyses involved more than 8,000 children from the nationwide É tude Longitudinale Française depuis l'Enfance (ELFE) birth cohort. Associations between family or infant history of allergy and frequency of OF consumption during the complementary feeding period were assessed with multinomial logistic regression. Associations between OF consumption in infancy and respiratory or allergic diseases between age 1 and 5.5 years were assessed with logistic regression.
Results: A family history of allergy or cow's milk protein allergy at age 2 months was strongly and positively related to feeding with OF during the complementary feeding period. Feeding with OF during the complementary feeding period was not related to respiratory diseases or eczema up to age 5.5 years. Compared to infrequent consumption of both organic and commercial complementary foods, frequent OF consumption without commercial complementary foods was associated with a higher risk of food allergy, whereas frequent commercial complementary food consumption without OF use was associated with a lower risk of food allergy.
Conclusions: This study suggests that a history of allergy strongly affects feeding with OF during the complementary feeding period. However, OF consumption was not associated with reduced odds of food allergy later in childhood but could be associated with increased odds, which should be examined more deeply.
... Previous research on the respiratory health of Swiss children focused on self-reported lower respiratory symptoms and a farming environment [8][9][10][11][12][13][14]. None of the recent population-based studies included a detailed assessment of lung function and airway inflammation. ...
... The gas mixture had the same molar mass (MM, g.mol-1) as medical-grade air, such that any detectable changes compared with normally expired molar mass can be attributed to relative changes in helium (He) and sulphur hexafluoride (SF 6) concentrations [9]. MM was measured by a side-stream ultrasonic flowmeter, tidal flows by a main-stream ultrasonic flowmeter. ...
... Quality control of DTG-SBW measurements was performed by the field workers on site. A double check of DTG-SBW test results is on-going, to see if the phase III was linear and constituted at least 50% of expired volume [9,12]. Quality control criteria for DTG-SBW were defined as: 1) no evidence of air leaks as monitored by volume and MM signals, 2) similar flow-volume-loops in pre-test and test breaths, 3) breath volumes of the five tidal pre-test and the test breaths were within 10%, 4) inspiratory peak flow within the by-pass flow. ...
Respiratory disease is common in children and strongly associated with lifestyle and environmental exposures. Thus, it is important to study the epidemiology locally. The LuftiBus in the School (LUIS) study was set up to assess the respiratory health of schoolchildren in the canton of Zurich, Switzerland.
LUIS is a cross-sectional population-based study that was carried out 2013 to 2016. Children aged 6–17 years living in the canton of Zurich were eligible to participate. All schools in the canton were approached and the school head decided whether the school would participate and with which classes. Consenting parents answered a standardised questionnaire at home and assenting children completed a shorter questionnaire by interview at school. Trained technicians measured children’s lung function, including spirometry, double tracer gas single-breath washout (DTG-SBW) and fractional exhaled nitric oxide (FeNO). Address histories of participants were geocoded to be linked with area-based socioeconomic measures and environmental exposures such as spatiotemporal air pollution estimates for specific time periods and locations. A subgroup was seen again 12 months later using the same procedures to collect longitudinal data.
The study included 3870 children at baseline and 655 at the 1-year follow-up. Median age was 12.7 years; 281 (8%) had wheezed in the past year. At baseline we collected 3457 (89%) parental and 3546 (92%) child questionnaires, and 3393 (88%) FeNO, 3446 (89%) spirometry, and 1795 (46%) DTG-SBW measurements.
LUIS is a rich resource of health-related data, with information on lung function, environmental exposures and respiratory health on Swiss schoolchildren.
... The European birth cohort PASTURE (Protection against Allergy: STUdy in Rural Environments), set up in the early 2000s, has focused on the protective effect of growing up on a dairy farm against Th2-driven allergic responses [5][6][7]. Up until now, several international cross-sectional studies have demonstrated that early farm exposure protects against allergic diseases, atopic sensitization, and asthma [8,9]. Early exposure during pregnancy and first years of life seems to be a window of opportunity for immune homeostasis [10]. ...
... Finally, not all farm environments protect against asthma and atopy [50]. In the past 20 years, traditional dairy farms have been studied in European cohorts to understand the specific factors of dairy farm environment involved in the protection of asthma and allergic diseases [5,8,9]. In addition to the exposure to a high endotoxin level, those studies have shown a protective effect of the consumption of raw cow's milk during pregnancy and in the first year of life [8] and also a protective effect of a diversity of early exposures [51], such as high food diversity [15] and exposure to different animal species [14]. ...
IntroductionOver the past 50 years, the prevalence of allergic respiratory diseases has been increasing. The Hygiene hypothesis explains this progression by the decrease in the bio-diversity of early microbial exposure. This study aims to evaluate the effect of early-life farm exposure on airway hyperresponsiveness and cough hypersensitivity in an allergic airway inflammation rabbit model.MethodA specific environment was applied to pregnant rabbits and their offspring until six weeks after birth. Rabbits were housed in a pathogen-free zone for the control group and a calf barn for the farm group. At the end of the specific environmental exposure, both groups were then housed in a conventional zone and then sensitized to ovalbumin. Ten days after sensitization, the rabbit pups received ovalbumin aerosols to provoke airway inflammation. Sensitization to ovalbumin was assessed by specific IgE assay. Cough sensitivity was assessed by mechanical stimulation of the trachea, and bronchial reactivity was assessed by methacholine challenge. The farm environment was characterized by endotoxin measurement.ResultsA total of 38 rabbit pups were included (18 in the farm group). Endotoxin levels in the farm environment varied from 30 to 1854 EU.m-3. There was no significant difference in specific IgE values to ovalbumin (p = 0.826) between the two groups. The mechanical threshold to elicit a cough did not differ between the two groups (p = 0.492). There was no difference in the number of cough (p = 0.270) or the intensity of ventilatory responses (p = 0.735). After adjusting for age and weight, there was no difference in respiratory resistance before and after methacholine challenge.Conclusion
Early exposure to the calf barn did not affect cough sensitivity or bronchial reactivity in ovalbumin-sensitized rabbits. These results suggest that not all farm environments protect against asthma and atopy. Continuous exposure to several sources of microbial diversity is probably needed.
... While the growing prevalence of AD, FA, and AR continues to be a concern, several studies have suggested that not all individuals may be at risk. Initial studies from Europe [86][87][88] and America [89,90] have demonstrated an association of rural/farm living and protection against sensitization and allergy. The most recent work is highlighted in Table 3. ...
... More recently, we found a lower prevalence of FA by 12 months in OOM compared to non-farming infants; the majority of the non-farm infants with FA were allergic to egg [97]. While there are examples demonstrating the protection of the rural/farm lifestyle against AD [87,88,100], there are several observations where it appears this environment did not confer protection [86,101,102]. Inconsistencies in this relationship can be due to variability in the type of rural or farm environment, types of farm animals, as well as whether studies examined the role of the maternal prenatal effect. ...
Purpose of Review
There has been an increased prevalence of allergy. Due to this relatively rapid rise, changes in environmental exposures are likely the main contributor. In this review, we highlight literature from the last 3 years pertaining to the role of air pollution, greenness, and the rural/farm lifestyle and their association with the development of allergic sensitization, atopic dermatitis, food allergy, and allergic rhinitis in infancy and childhood. Because asthma has a more complex pathophysiology, it was excluded from this review.
Recent Findings
Recent studies support a role for air pollution, greenness, and rural/farming lifestyle influencing atopic outcomes that continue to be defined. While many studies have examined singular environmental exposures, the interconnectedness of these exposures and others points to a need for future work to consider an individual’s whole exposure.
Summary
Environmental exposures’ influence on atopic disease development remains an ongoing and important area of study.
... Agronomie, 23, 1-4. Turk, M. A., Tawaha, A. M., & Shatnawi, M., (2003a Van, B. A. H., (2006) Van, D. H. M. G., (2017). Cover crops support ecological intensification of arable cropping systems. ...
... • Reduction of allergies among children (5-13) through the consumption of organic foods according to the cross-sectional PARSIFAL study by Alfvén et al. (2006) and confirmed by Stenius (2011). • Lowered risk of eczema at 2 years among babies who consumed organic daily products according to the KOALA study by Alim et al. (1999); and Kummeling (2008). ...
Global climate changes such as increasing CO2 levels, temperature increases,
drought, etc., have been shown to adversely affect agricultural products.
Weeds can be seen as a major problem because they seem to fight at the
expense of the crop for resources such as light, water, and nutrients. Weed
species are commonly favored in crops that are more closely associated with
them. The association between weeds and crops is due to their similar growth
habits. The basic strategy should be considered as the core of the organic
weed control strategy: crop stand, crop rotation, crop cover, variety selection,
clean seeds, soil health, soil structure, spring tillage, delayed planting,
post-emergence tillage, hand weeding, mulches, and organic herbicides.
This chapter focuses on: (i) classification of weed species; and (ii) weed
management strategies under climate change.
... Agronomie, 23, 1-4. Turk, M. A., Tawaha, A. M., & Shatnawi, M., (2003a Van, B. A. H., (2006) Van, D. H. M. G., (2017). Cover crops support ecological intensification of arable cropping systems. ...
... • Reduction of allergies among children (5-13) through the consumption of organic foods according to the cross-sectional PARSIFAL study by Alfvén et al. (2006) and confirmed by Stenius (2011). • Lowered risk of eczema at 2 years among babies who consumed organic daily products according to the KOALA study by Alim et al. (1999); and Kummeling (2008). ...
Azospirillum Bioinoculant Technology: Past to Current Knowledge and
Future Prospects
Palani Saranraj, Abdel Rahman Mohammad Al–Tawaha,
Panneerselvam Sivasakthivelan, Abdel Razzaq M. Altawaha,
Kangasalam Amala, Devarajan Thangadurai, and
Jeyabalan Sangeetha
... Agronomie, 23, 1-4. Turk, M. A., Tawaha, A. M., & Shatnawi, M., (2003a Van, B. A. H., (2006) Van, D. H. M. G., (2017). Cover crops support ecological intensification of arable cropping systems. ...
... • Reduction of allergies among children (5-13) through the consumption of organic foods according to the cross-sectional PARSIFAL study by Alfvén et al. (2006) and confirmed by Stenius (2011). • Lowered risk of eczema at 2 years among babies who consumed organic daily products according to the KOALA study by Alim et al. (1999); and Kummeling (2008). ...
PART III: ORGANIC AGRICULTURE FOR FOOD
SAFETY
13. Organic Production Technology of Rice
Shah Khalid, Amanullah, Nadia, Imranuddin,
Mujeeb Ur Rahman, Abdel Rahman Al Tawaha,
Devarajan Thangadurai, Jeyabalan Sangeetha,
Samia Khanum, Munir Turk, Hiba Alatrash,
Sameena Lone, Khursheed Hussain, Palani Saranraj, and Arun
Karnwal
... Agronomie, 23, 1-4. Turk, M. A., Tawaha, A. M., & Shatnawi, M., (2003a Van, B. A. H., (2006) Van, D. H. M. G., (2017). Cover crops support ecological intensification of arable cropping systems. ...
... • Reduction of allergies among children (5-13) through the consumption of organic foods according to the cross-sectional PARSIFAL study by Alfvén et al. (2006) and confirmed by Stenius (2011). • Lowered risk of eczema at 2 years among babies who consumed organic daily products according to the KOALA study by Alim et al. (1999); and Kummeling (2008). ...
... A significant improvement of 60% (p = 0.0034) in the primary endpoint TNSS (V1 2.5 [interquartile range, IQR 1-4], V3 1.0 [IQR 1-3]) was observed. 40% improvement was seen for the Total Symptom Score (V1 5.0 [IQR [3][4][5][6][7][8][9], V3 3.0 [IQR [2][3][4]; [Wilcoxon test: confidence interval 1.5-4.0, p < 0.0003]). ...
... However, luckily already discovered and intensively discussed, there is a known protective phenomenon called the farm effect [2][3][4][5]. As shown in several earlier studies [6][7][8][9], childbearing and growing up on a traditional farm with dairy farming provides protection against allergic sensitization, asthma, and hay fever. These diseases have been shown to occur at a much lower frequency in farm children compared to children from urban re-gions [10][11][12]. ...
Evaluation of a lozenge for targeted micronu-trition (holo-BLG), a new invention based on the farm effect, in house dust mite (HDM) allergic rhinocon-junctivitis (ARC) patients in a standardized allergen exposure chamber (AEC).
Eligible HDM allergic patients were exposed to HDM raw material in an AEC for 120 min before (V1) and after (V3) 3 months of holo-BLG supple-mentation. Nasal, conjunctival, bronchial and other symptoms were rated by the patients every 10 min and, wellbeing, peak nasal inspiratory flow (PNIF), and lung function parameters every 30 min. Primary endpoint was the change in median Total Nasal Symptom Score (TNSS) at V3 compared to V1 at 120 min of exposure. Secondary endpoints consisted of the exploratory
analysis of the temporal evolution of symptom scores using linear mixed effects models.
A total of 32 patients were included in the analysis. A significant improvement of 60% (p= 0.0034) in the primary endpoint TNSS (V1 2.5 [interquartile range, IQR 1–4], V3 1.0 [IQR 1–3]) was observed. 40% improvement was seen for the Total Symptom Score (V1 5.0 [IQR 3–9], V3 3.0 [IQR 2–4]; [Wilcoxon test: confidence interval 1.5–4.0, p<0.0003]). The analysis of the temporal evolution of all symptom scores and the personal wellbeing revealed clinically meaningful improvement over time, manifested in a lower symptom increase during the final HDM exposure. No relevant differences were observed for PNIF and lung function parameters. Safety and tolerability were rated as excellent.
The effect of holo-BLG resulting in immune resilience might help to fight the allergy epidemic on a new front based on targeted micronutrition of immune cells.
... 1 The vast increase in the prevalence of allergic diseases is mainly evident in industrialized countries and is often linked to the Western lifestyle. 2,3 This lifestyle is accompanied by the loss of rural living conditions resulting in a decreased microbial exposure in early life. In accordance with this socalled hygiene hypothesis, epidemiological studies have consistently shown that children growing up on a farm are at a significantly lower risk of developing allergic diseases than children living in the same rural area but not growing up on a farm. ...
... In accordance with this socalled hygiene hypothesis, epidemiological studies have consistently shown that children growing up on a farm are at a significantly lower risk of developing allergic diseases than children living in the same rural area but not growing up on a farm. [3][4][5][6][7][8][9] Several farm exposures have been associated with this protective 'farm effect', [10][11][12][13] but particularly the consumption of raw, unprocessed, cow's milk is of interest, since this effect was found to be independent of living on a farm. This suggests that a general, non-farming, population might equally benefit from the consumption of raw cow's milk. ...
The allergy-protective capacity of raw cow's milk was demonstrated to be abolished after heat treatment. The heat-sensitive whey protein fraction of raw milk is often implied to be the source of this allergy-protective effect, but a direct link between these proteins and the protection against allergic diseases is missing. This study therefore aimed at investigating the mechanistic relation between heat damage to whey proteins and allergy development. Raw cow's milk was heated for 30 min at 50, 60, 65, 70, 75, or 80 °C and the native whey protein profile of these differentially heated milk samples was determined using LC-MS/MS-based proteomics. Changes in the native protein profile were subsequently related to the capacity of these milk samples to prevent the development of ovalbumin-induced food allergy in a murine animal model. A substantial loss of native whey proteins, as well as extensive protein aggregation, was observed from 75 °C. However, whey proteins with immune-related functionalities already started to denature from 65 °C, which coincided with the temperature at which a loss of allergy protection was observed in the murine model. Complement C7, monocyte differentiation antigen CD14, and polymeric immunoglobulin receptor concentrations decreased significantly at this temperature, although several other immunologically active whey proteins also showed a decrease around 65 °C. The current study demonstrates that immunologically active whey proteins that denature around 65 °C are of importance for the allergy-protective capacity of raw cow's milk and thereby provides key knowledge for the development of microbiologically safe alternatives to raw cow's milk.
... As early as the late 1990s, Von Ehrenstein and colleagues [41] as well as Riedler and colleagues [42,43] found that farmer's children have a lower prevalence of hay fever, asthma, rhinoconjunctivitis as well as other atopic diseases and concluded that increased exposure to bacterial compounds in stables with livestock prevents the development of allergic disorders in children (level III). These findings could also be reproduced in other authors [see, e.g., [44][45][46][47][48]. There is a solid body of evidence that exposure to a greater variety of environmental microorganisms explains a substantial fraction of the inverse relation between asthma and growing up on a farm [49]. ...
Alpine regions are characterized by exceptional natural resources, cultural heritage,
healthy climate, and long tourism tradition. Tourism is a major component of
economic growth, with several employment opportunities, and of great importance
for the Alpine regions, with many positive effects on the local and regional population.
Natural resources can determine the development of competitive tourism destinations and drive the development of nature-based value chains aimed at enhancing
tourists’ health and well-being. Historically, the small size of most enterprises,
the difficulties in establishing collaborative relationships between industry operators, and the lack of strategic projects aimed at the use and exploitation of natural
resources, have hindered a systematic development of a nature-based health tourism
(NHT) value chain. Nowadays, tourist market segments are changing the industry
competitiveness with the request for more nature-based experiential programs, integrating both rewarding elements of beauty, relaxation, and regeneration, and more
demanding elements such as preventative activities and sports. There is an increasing
consciousness of the importance of local environmental and cultural preservation,
the search for relax and stress-relieving products, and the overall authenticity of
the vacation experience. Beyond lifestyle changes, key trends reshaping the health
tourism landscape in Alpine regions include population ageing, climate change, and
consequences of the COVID-19 pandemic both in terms of business losses and the
need for natural remedies against these virus’s long-term effects.
This background challenges health tourism operators to rethink the industry
dynamics with a more innovation-driven strategy and business development, as well
as facilitation of transnational cooperation among all kinds of actors. These include
sectoral and specialized agencies such as destination management organizations,
business support organizations, and tourism organizations; regional councils and
municipalities in charge of policy-making and tourism strategy development; tourism
facilities and companies (especially small- and medium-sized enterprises); universities and research centres that conduct applied research and development within the
health tourism sector and related sectors, based on natural resources or health-related
issues; interest groups and networks supporting nature-based and sustainable health
tourism. Despite the richness of natural resources and health-promoting activities that spread among Alpine regions, the NHT landscape is characterized by innovation
spatial fragmentation, lack of access to knowledge, and little transversal cooperation
for value creation and sharing.
Aimed to address these key territorial challenges, the HEALPS2 project “Healing
Alps: Tourism based on natural health resources as strategic innovation for the development of Alpine regions” was funded in the Priority “Innovative Alpine Space” of
the Interreg Alpine Space program. The key objective of the project was to improve
the framework conditions for utilizing the Alpine natural health resources by leveraging existing and newly developed NHT products and service chains to enhance
access to knowledge and sharing of experiences at a transnational level. The main
project activities took place from October 2019 to June 2022 and involved 11 organizations from 6 countries, i.e. Austria, Italy, Slovenia, Germany, France, and Switzerland. The collaboration between the project partners led to the development of a set of
innovation practices and digital solutions, properly combined with the latest research
results in tourism and health-related issues and the requirements of health tourism
stakeholders collected in several events organized at the local and regional level. The
vision of the project is to contribute to the positioning of the Alpine Space as a globally attractive health-promoting place, with a virtuous process of value generation
and sharing among Alpine assets, actors, and territories.
This book incorporates the key knowledge and experiences, in terms of concepts,
tools, and practices, developed within the HEALPS2 project, here organized into
eight chapters. The content was purposefully organized to dedicate to the core assets
for an Alpine NHT industry excellence, i.e. the natural resources and their healing
effects; the digital tools enhancing the collection, advanced analytics and spread
of data on NHT industry for supporting strategic decision-making; the innovation
practices and communication strategies to properly engage the industry stakeholders.
... As early as the late 1990s, Von Ehrenstein and colleagues [41] as well as Riedler and colleagues [42,43] found that farmer's children have a lower prevalence of hay fever, asthma, rhinoconjunctivitis as well as other atopic diseases and concluded that increased exposure to bacterial compounds in stables with livestock prevents the development of allergic disorders in children (level III). These findings could also be reproduced in other authors [see, e.g., [44][45][46][47][48]. There is a solid body of evidence that exposure to a greater variety of environmental microorganisms explains a substantial fraction of the inverse relation between asthma and growing up on a farm [49]. ...
Tourism has been one of the most important economic sectors in the Alps for many years. However, not least because of the cuts due to the pandemic, new and innovative approaches are needed to meet current challenges such as climate change, shortage of skilled workers or demographic change in order to make Alpine tourism fit for the future. The topic of health offers great potential in this context. With the KPI approach, therefore, a possible access to a nature-based health tourism with medical evidence is presented, which should support the actors from the tourism practice in the further development of the Alpine tourism. At the same time, the KPI approach also offers possibilities to enable an overall more sustainable development of the Alpine region. This paper places the KPI approach in a larger development framework and explains the underlying analytical system based on selected indicators.
... As early as the late 1990s, Von Ehrenstein and colleagues [41] as well as Riedler and colleagues [42,43] found that farmer's children have a lower prevalence of hay fever, asthma, rhinoconjunctivitis as well as other atopic diseases and concluded that increased exposure to bacterial compounds in stables with livestock prevents the development of allergic disorders in children (level III). These findings could also be reproduced in other authors [see, e.g., [44][45][46][47][48]. There is a solid body of evidence that exposure to a greater variety of environmental microorganisms explains a substantial fraction of the inverse relation between asthma and growing up on a farm [49]. ...
This work describes the challenges, techniques, and methodologies to develop a digital tool that aims to improve framework conditions and tools for better utilization of Alpine natural resources in health tourism. Starting from the literature analysis and an online survey, the system implemented a comprehensive knowledge base adopted for an ontology-based Decision Support System leveraging on identified Key Performance Indicators (KPIs). Relying on this knowledge, the digital tool provides a list of tailored and customized recommendations for each destination within the Alpine area. This result helps the stakeholders capitalize on the nature-based health tourism potentials of their region in relation to the existence of the natural resources and different target users’ health conditions. This strategic digital tool is developed as a web-based application for destinations’ policy-makers and managers to fill the online survey and receive customized suggestions, recommendations, and insights on how to further exploit their natural resources in order to enhance nature-based health tourism.
... As early as the late 1990s, Von Ehrenstein and colleagues [41] as well as Riedler and colleagues [42,43] found that farmer's children have a lower prevalence of hay fever, asthma, rhinoconjunctivitis as well as other atopic diseases and concluded that increased exposure to bacterial compounds in stables with livestock prevents the development of allergic disorders in children (level III). These findings could also be reproduced in other authors [see, e.g., [44][45][46][47][48]. There is a solid body of evidence that exposure to a greater variety of environmental microorganisms explains a substantial fraction of the inverse relation between asthma and growing up on a farm [49]. ...
The Alpine space disposes of excellent prerequisites to respond to the increasing demand of nature-based health tourism. Despite a growing scientific knowledge on the manifold benefits of human interaction with Alpine natural resources, the health tourism potential has not yet been fully exploited by Alpine regions. Based on major push and pull factors, the current state of scientific knowledge on the healing potential of nine selected natural Alpine resources is presented and discussed with regard to their health tourism potential. Major research gaps as well as starting points for future studies are demonstrated. In this way, the present work contributes to an applicable knowledge base on the health benefits of Alpine resources to enhance regional innovation capacity in terms of sustainable health tourism development. As tourism regions are increasingly taking evidence-based approaches to health tourism and regional development, the resulting lighthouses will contribute to the positioning of the Alpine space as globally attractive healing environment.
... As early as the late 1990s, Von Ehrenstein and colleagues [41] as well as Riedler and colleagues [42,43] found that farmer's children have a lower prevalence of hay fever, asthma, rhinoconjunctivitis as well as other atopic diseases and concluded that increased exposure to bacterial compounds in stables with livestock prevents the development of allergic disorders in children (level III). These findings could also be reproduced in other authors [see, e.g., [44][45][46][47][48]. There is a solid body of evidence that exposure to a greater variety of environmental microorganisms explains a substantial fraction of the inverse relation between asthma and growing up on a farm [49]. ...
Participatory stakeholder engagement in strategy-making, for industries such as Nature-based Health Tourism (NHT), enhances the delivery of more useful and applicable strategies, with also higher chances to reach intended goals if compared to conventional top-down planning processes. This chapter describes the methodology identified and carried out in the HEALPS2 project to efficiently reach and engage stakeholders of Alpine NHT and to form a stakeholder group at the transnational level (including the engagement of EU-level ac-tors and networks). Based on the Quadruple Helix concept, the methodology integrates a process of stakeholder engagement and endorsement along three steps; the identification of the key points and the problems to be tackled for a successful stakeholder engagement; and the development of Regional and Transnational Stakeholder Groups that extend to the cooperation with EU-wide networks. Developing health tourism products and service chains, and sustaining them with strategies and policies, is a complex undertaking. The adoption of the stakeholder engagement approaches throughout the HEALPS2 project showed that it is of utmost importance to properly identify, involve and communicate with the stakeholders who effectively complement the success of the project, and its outcomes, in enhancing NHT competitiveness.
... As early as the late 1990s, Von Ehrenstein and colleagues [41] as well as Riedler and colleagues [42,43] found that farmer's children have a lower prevalence of hay fever, asthma, rhinoconjunctivitis as well as other atopic diseases and concluded that increased exposure to bacterial compounds in stables with livestock prevents the development of allergic disorders in children (level III). These findings could also be reproduced in other authors [see, e.g., [44][45][46][47][48]. There is a solid body of evidence that exposure to a greater variety of environmental microorganisms explains a substantial fraction of the inverse relation between asthma and growing up on a farm [49]. ...
Communication activities play a pivotal role in the management of research projects, especially those involving several partners and stakeholders from different countries. The Interreg Alpine Space HEALPS2 project relies on a transnational and transversal approach to improve the framework conditions and tools for alpine health tourism, and therefore proposes a communication strategy based on specific objectives. These objectives guide the communication activities at an internal and external level, with the latter being declined for different targets and stakeholders. In this Chapter, the communication activities are described, starting from the general and specific objectives-oriented approach, to the local realization. The general strategy and the analysis are illustrated, then are demonstrated through a regional use case—the Parco Regionale Alpe Veglia-Alpe Devero and Parco Regionale Alta Valle Antrona.
... As early as the late 1990s, Von Ehrenstein and colleagues [41] as well as Riedler and colleagues [42,43] found that farmer's children have a lower prevalence of hay fever, asthma, rhinoconjunctivitis as well as other atopic diseases and concluded that increased exposure to bacterial compounds in stables with livestock prevents the development of allergic disorders in children (level III). These findings could also be reproduced in other authors [see, e.g., [44][45][46][47][48]. There is a solid body of evidence that exposure to a greater variety of environmental microorganisms explains a substantial fraction of the inverse relation between asthma and growing up on a farm [49]. ...
Innovation is considered essential to the growth and long-term sustainability of health tourism companies and destinations. Continuous innovation takes place to improve the industry competitiveness, but especially the tourists’ experience and wellness with new product offerings. This Chapter collects and describes the innovation practices proposed and developed in some pilot regions of the HEALPS2 project consortium. The innovation practices identified in the project can be subdivided into three types, i.e., innovation techniques, innovation supporting tools, and innovative product offerings. All the practices were designed to target several operators of the Nature-based Health Tourism (NHT) industry, from tourism facilities and companies (especially small- and medium-sized enterprises) to regional councils and municipalities in charge of policy-making and tourism strategy development. HEALPS 2 innovation practices and techniques can be purposefully integrated at the regional and local level for a more innovation-driven industry strategy and business development, as well as facilitation of transnational cooperation among key actors, also beyond Alpine regions and NHT destinations.
... As early as the late 1990s, Von Ehrenstein and colleagues [41] as well as Riedler and colleagues [42,43] found that farmer's children have a lower prevalence of hay fever, asthma, rhinoconjunctivitis as well as other atopic diseases and concluded that increased exposure to bacterial compounds in stables with livestock prevents the development of allergic disorders in children (level III). These findings could also be reproduced in other authors [see, e.g., [44][45][46][47][48]. There is a solid body of evidence that exposure to a greater variety of environmental microorganisms explains a substantial fraction of the inverse relation between asthma and growing up on a farm [49]. ...
Nature-based health tourism is experiencing a resurgence. To determine its potential as a development opportunity for alpine destinations, it is necessary to analyse both the demand and supply side. Two surveys were conducted: a representative survey of the population of six countries of the Alpine Space exploring the perception of the Alps as a healthy destination in general and on the personal assessment of the health effect of natural resources in particular and an exploratory survey of tourism stakeholders in destination management, accommodation and gastronomy as well as (health) tourism services with a focus on the expected economic developments and the relevance of individual target groups for nature-based health tourism. The results demonstrate the need for a strategic development process which aligns perceptions with destination strategy and pre-existing offers. Two potential strategies are briefly outlined: 1. destinations with non-locally specific alpine natural health resources can develop broad tourism experiences for health conditions that occur across society with health a secondary aspect in marketing. 2. destinations featuring locally specific natural health resources with proven evidence can develop offers for a specific condition and are thus able to target a very specific group.
... As early as the late 1990s, Von Ehrenstein and colleagues [41] as well as Riedler and colleagues [42,43] found that farmer's children have a lower prevalence of hay fever, asthma, rhinoconjunctivitis as well as other atopic diseases and concluded that increased exposure to bacterial compounds in stables with livestock prevents the development of allergic disorders in children (level III). These findings could also be reproduced in other authors [see, e.g., [44][45][46][47][48]. There is a solid body of evidence that exposure to a greater variety of environmental microorganisms explains a substantial fraction of the inverse relation between asthma and growing up on a farm [49]. ...
The competitiveness of nature-based Health Tourism (NHT) industry, especially in the Alpine regions, is increasingly linked to the sustainability and exploitation of unique natural resources of tourism destinations, which often lack the access to knowledge and networks of stakeholders to improve their offerings. In this sense, the use of digital tools can open up further opportunities to reconsider value offerings and better access different knowledge resources and relationships within the industry network. This Chapter illustrates the collaborative design approach adopted in HEALPS2 for the development of an ontology-based Decision Support System for health tourism destinations. The resulting ontology aims to model the relationships between the available natural resources, the value offerings and the target groups of NHT destinations. Moreover, the Collaborative Design approach foresees the involvement of end-users (i.e. not only tourism destinations, but also the network of stakeholders, and the actual and potential future tourists) as both sources of knowledge and validators of the ontology and its outputs, aiming to inform decision-making processes in a shared knowledge model that leverages on digital tools.
... Well-functioning immune regulation and immune tolerance and low incidence of immune-mediated diseases has been reported to be associated with living next to agricultural areas and green space (Hanski et al., 2012;Kirjavainen et al., 2019;Nurminen et al., 2021). Similarly, people following traditional lifestyles with abundant contacts with environmental microbiota typically have diverse commensal microbiota and low incidences of immune-mediated diseases (Alfven et al., 2006;Kondrashova et al., 2013;Lee et al., 2012;Stein et al., 2016;Williams et al., 2005). On the other hand, agricultural environment may enrich bacteria, such as Thermoactinomyces vulgaris, T. viridis and T. sacchari, that have been associated with inflammatory reactions and eventually hypersensitivity pneumonitis (Nogueira et al., 2019). ...
Background: According to the biodiversity hypothesis of immune-mediated diseases, lack of microbiological diversity in the everyday living environment is a core reason for dysregulation of immune tolerance and – eventually – the epidemic of immune-mediated diseases in western urban populations. Despite years of intense research, the hypothesis was never tested in a double-blinded and placebo-controlled intervention trial. Objective: We aimed to perform the first placebo-controlled double-blinded test that investigates the effect of biodiversity on immune tolerance. Methods: In the intervention group, children aged 3–5 years were exposed to playground sand enriched with microbially diverse soil, or in the placebo group, visually similar, but microbially poor sand colored with peat (13 participants per treatment group). Children played twice a day for 20 min in the sandbox for 14 days. Sand, skin and gut bacterial, and blood samples were taken at baseline and after 14 days. Bacterial changes were followed for 28 days. Sand, skin and gut metagenome was determined by high throughput sequencing of bacterial 16 S rRNA gene. Cytokines were measured from plasma and the frequency of blood regulatory T cells was defined as a percentage of total CD3 +CD4 + T cells. Results: Bacterial richness (P
... Children growing up on farms have a lower risk of asthma and allergies than children living in the same rural area but not on farms [89,90]. This protective "farm effect" is recognized in many people until adulthood [91]. ...
Alkaline phosphatase (ALP) is abundant in raw milk. Because of its high heat resistance, ALP negative is used as an indicator of successful sterilization. However, pasteurized milk loses its immune protection against allergy. Clinically, ALP is also used as an indicator of organ diseases. When the activity of ALP in blood increases, it is considered that diseases occur in viscera and organs. Oral administration or injecting ALP will not cause harm to the body and has a variety of probiotic effects. For infants with low immunity, ALP intake is a good prebiotic for protecting the infant’s intestine from potential pathogenic bacteria. In addition, ALP has a variety of probiotic effects for any age group, including prevention and treatment intestinal diseases, allergies, hepatitis, acute kidney injury (AKI), diabetes, and even the prevention of aging. The prebiotic effects of alkaline phosphatase on the health of infants and consumers and the content of ALP in different mammalian raw milk are summarized. The review calls on consumers and manufacturers to pay more attention to ALP, especially for infants with incomplete immune development. ALP supplementation is conducive to the healthy growth of infants.
... Taking organic level in the diets, organic consumers who regularly buy and consume organic food are healthier with markedly less overweight and obesity Eisinger-Watzl et al., 2015) as well as following recommended healthier dietary patterns (Kesse- Baudry et al., 2016aBaudry et al., , 2016b. Other studies reported reduced allergy prevalence in children following an organic diet (Alfven et al., 2006) or a reduced risk of having a metabolic syndrome in adults (Baudry et al., 2017a, b). ...
Sustainable diets are those diets with low environmental impacts that contribute to food and nutrition security and to healthy lives for present and future generations. Sustainable diets are protective and respectful of biodiversity and ecosystems, culturally acceptable, accessible, economically fair and affordable, are nutritionally adequate, safe, and healthy, and optimize natural and human resources. (FAO, 2010).
This book takes a transdisciplinary approach and considers multisectoral actions, integrating health, agriculture and environmental sector issues to comprehensively explore the topic of sustainable diets.
The team of international authors informs readers with arguments, challenges, perspectives, policies, actions and solutions on global topics that must be properly understood in order to be effectively addressed. They position issues of sustainable diets as central to the Earth’s future. Presenting the latest findings, they:
• Explore the transition to sustainable diets within the context of sustainable food systems, addressing the right to food, and linking food security and nutrition to sustainability.
• Convey the urgency of coordinated action, and consider how to engage multiple sectors in dialogue and joint research to tackle the pressing problems that have taken us to the edge, and beyond, of the planet’s limits to growth.
• Review tools, methods and indicators for assessing sustainable diets.
• Describe lessons learned from case studies on both traditional food systems and current dietary challenges.
As an affiliated project of the One Planet Sustainable Food Systems Programme, this book provides a way forward for achieving global and local targets, including the Sustainable Development Goals and the United Nations Decade of Action on Nutrition commitments. This resource is essential reading for scientists, practitioners, and students in the fields of nutrition science, food science, environmental sciences, agricultural sciences, development studies, food studies, public health and food policy
... In one cross-sectional study, frequent consumption of fermented vegetables, a characteristic of the anthroposophic lifestyle, was correlated with lower prevalence of allergic diseases and positive responses to objective tests of atopy in children [144]. The lower prevalence of current rhinoconjunctivitis symptoms, atopic eczema symptoms, and atopic sensitization was also reported among children attending Steiner schools leading an anthroposophic lifestyle in the PARSIFAL study [145]. Similar findings have also been found in the prospective birth cohort Assessment of Lifestyle and Allergic Disease During Infancy (ALADDIN), which demonstrated that leading an anthroposophic lifestyle was associated with a decreased prevalence of food allergen sensitization and episodes of wheeze reported by parents, but not eczema [146]. ...
In the last few decades, a dramatic increase in the global prevalence of allergic diseases and asthma was observed. It was hypothesized that diet may be an important immunomodulatory factor influencing susceptibility to allergic diseases. Fermented food, a natural source of living microorganisms and bioactive compounds, has been demonstrated to possess health-promoting potentials and seems to be a promising strategy to reduce the risk of various immune-related diseases, such as allergic diseases and asthma. The exact mechanisms by which allergic diseases and asthma can be alleviated or prevented by fermented food are not well understood; however, its potential to exert an effect through modulating the immune response and influencing the gut microbiota has been recently studied. In this review, we provide the current knowledge on the role of diet, including fermented foods, in preventing or treating allergic diseases and asthma.
... Авторы обнаружили, что у детей, живущих в сельскохозяйственной среде, частота сенной лихорадки, астмы и экземы значительно снижена по сравнению с детьми, проживающими в городских районах. Аналогичная взаимосвязь была продемонстрирована также по данным исследований PARSIFAL [22] и GABRIELA [23], которые подтвердили предыдущие наблюдения о том, что дети, живущие на фермах, имеют сниженный уровень аллергических заболеваний по сравнению с городскими детьми. Хотя в большинстве подобного рода исследований основное внимание уделялось влиянию постнатального воздействия окружающей среды, сегодня все больше доказательств того, что важное значение может иметь и предродовое воздействие [24]. ...
The review article presents current data on the possible connection between the occurrence of allergies and disorders in the intestinal microbiota. The role of the intestinal microbiota in the development of the immune system of a child, as well as the maintenance of its immune tolerance, is discussed. Factors whose effects can be associated with changes in the intestinal microbiota and the development of allergic diseases are considered.
... The "hygiene hypothesis" proposed that respiratory infections associated with overcrowding and unhygienic conditions confer an element of protection on hay fever and atopy. 51 The hypothesis has been pushed forward by various comparative studies conducted in different regions across the globe showing that children living in a rural/farming environment had much lower prevalence of allergies than those in urban areas, [52][53][54][55][56][57][58] representing one of the strongest and most consistent protective factors against development of allergic diseases. Two main pillars of the "farm effect" in central Europe are exposure to livestock and consumption of raw farm milk. ...
Asia-Pacific is a populous region with remarkable variations in socioeconomic development and environmental exposure among countries. The prevalence rates of asthma and allergic rhinitis appear to have recently reached a plateau in Western countries, whereas they are still increasing in many Asian countries. Given the large population in Asia, even a slight increase in the prevalence rate will translate into an overwhelming number of patients. To reduce the magnitude of the increase in allergic diseases in next few decades in Asia, we must understand the potential factors leading to the occurrence of these disorders and the development of potential preventive strategies. The etiology of allergic disorders is likely due to complex interactions among genetic, epigenetic, and environmental factors for the manifestations of inappropriate immune responses. As urbanization and industrialization inevitably progress in Asia, there is an urgent need to curtail the upcoming waves of the allergy epidemic. Potentially modifiable risk exposure, such as air pollution, should be minimized through timely implementation of effective legislations. Meanwhile, re-introduction of protective factors that were once part of the traditional farming lifestyle might give new insight into primary prevention of allergy.
... According to Alfvén et al. 4 Kummeling et al. 5 several studies have examined the possible human health effects of organic diets through observational data from consumers beyond the chemical composition of foods. A few studies suggest that the consumption of organic foods can be associated with a lower risk of allergies and eczema in infants. ...
... Atopic diseases have increased in the last decades [121], especially in developed countries. Genetic and environmental factors have a crucial role in this condition; in this regard, the "hygiene hypothesis" [122] assumes that reduced early life exposure to factors contributing to the modulation and maturation of the immune system, as the contact and infection with different microbes could increase the risk of developing atopic diseases [123]. As it is known, the gut microbiota is one of the most important contributors to the development and maintenance of immune system functions. ...
Bifidobacteria are among the predominant microorganisms during infancy, being a dominant microbial group in the healthy breastfed infant and playing a crucial role in newborns and infant development. Not only the levels of the Bifidobacterium genus but also the profile and quantity of the different bifidobacterial species have been demonstrated to be of relevance to infant health. Although no definitive proof is available on the causal association, reduced levels of bifidobacteria are perhaps the most frequently observed alteration of the intestinal microbiota in infant diseases. Moreover, Bifidobacterium strains have been extensively studied by their probiotic attributes. This review compiles the available information about bifidobacterial composition and function since the beginning of life, describing different perinatal factors affecting them, and their implications on different health alterations in infancy. In addition, this review gathers exhaustive information about pre-clinical and clinical studies with Bifidobacterium strains as probiotics in neonates.
... For example, a study of Swedish children found significantly higher risk of allergic conditions among those from public schools than for those at nearby Steiner schools catering to families that emphasized a biodynamic, vegetablerich organic diet (Alm, 1999). Another comparison, involving almost 15,000 European children, found those from public schools who ate more conventional diets had higher incidences of asthma and food allergies (Alfven et al., 2006). A pair of Danish studies reported sperm counts were highest among men who consumed the most organic produce and lowest among those who consumed only conventional produce (Jensen et al., 1996;Juhler et al., 1999). ...
Controversy has long surrounded the question of nutritional differences between crops grown organically or using now-conventional methods, with studies dating back to the 1940s showing that farming methods can affect the nutrient density of crops. More recent studies have shown how reliance on tillage and synthetic nitrogen fertilizers influence soil life, and thereby soil health, in ways that can reduce mineral micronutrient uptake by and phytochemical production in crops. While organic farming tends to enhance soil health and conventional practices degrade it, relying on tillage for weed control on both organic and conventional farms degrades soil organic matter and can disrupt soil life in ways that reduce crop mineral uptake and phytochemical production. Conversely, microbial inoculants and compost and mulch that build soil organic matter can increase crop micronutrient and phytochemical content on both conventional and organic farms. Hence, agronomic effects on nutritional profiles do not fall out simply along the conventional vs. organic distinction, making the effects of farming practices on soil health a better lens for assessing their influence on nutrient density. A review of previous studies and meta-studies finds little evidence for significant differences in crop macronutrient levels between organic and conventional farming practices, as well as substantial evidence for the influence of different cultivars and farming practices on micronutrient concentrations. More consistent differences between organic and conventional crops include that conventional crops contain greater pesticide levels, whereas organically grown crops contain higher levels of phytochemicals shown to exhibit health-protective antioxidant and anti-inflammatory properties. Thus, part of the long-running controversy over nutritional differences between organic and conventional crops appears to arise from different definitions of what constitutes a nutrient—the conventional definition of dietary constituents necessary for growth and survival, or a broader one that also encompasses compounds beneficial for maintenance of health and prevention of chronic disease. For assessing the effects of farming practices on nutrient density soil health adds a much needed dimension—the provisioning of micronutrients and phytochemicals that support human health.
... 20,34,35 The OR of 0.49 in our study was similar in magnitude to that reported in studies from suburban Europe (OR 0.49) and alpine areas (OR 0.74). 36,37 The childhood farming environment is related to higher expression levels of innate immunity genes and protects against asthma development during childhood. 21 In an earlier study, long-term and early-life exposure to stables and farm milk was associated with the highest protective effect against asthma development in children. ...
Purpose:
Asthma is a heterogeneous disease, and factors associated with different asthma phenotypes are poorly understood. Given the higher prevalence of farming exposure and late diagnosis of asthma in more rural Western Finland as compared with the capital of Helsinki, we investigated the relationship between childhood farming environment and age at asthma diagnosis.
Methods:
A cross-sectional population-based study was carried out with subjects aged 20-69 years in Western Finland. The response rate was 52.5%. We included 3864 participants, 416 of whom had physician-diagnosed asthma at a known age and with data on the childhood environment. The main finding was confirmed in a similar sample from Helsinki. Participants were classified as follows with respect to asthma diagnosis: early diagnosis (0-11 years), intermediate diagnosis (12-39 years), and late diagnosis (40-69 years).
Results:
The prevalence of asthma was similar both without and with childhood exposure to a farming environment (11.7% vs 11.3%). Allergic rhinitis, family history of asthma, ex-smoker, occupational exposure, and BMI ≥ 30 kg/m2 were associated with a higher likelihood of asthma. Childhood exposure to a farming environment did not increase the odds of having asthma (aOR, 1.10; 95% CI, 0.87-1.40). It did increase the odds of late diagnosis (aOR, 2.30; 95% CI, 1.12-4.69), but the odds were lower for early (aOR, 0.49; 95% CI, 0.30-0.80) and intermediate diagnosis of asthma (aOR, 0.75; 95% CI, 0.47-1.18).
Conclusion:
Odds were lower for early diagnosis of asthma and higher for late diagnosis of asthma in a childhood farming environment. This suggests a new hypothesis concerning the etiology of asthma when it is diagnosed late.
... Diverse microbial exposure in children growing up on traditional cattle farms has also been linked to reduced persistent wheezing and asthma risk [166,167]. Two crosssectional studies have looked at children living in rural farming communities in Central Europe, the German PARSIFAL (Prevention of Allergy-Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle) study [168], and Bavarian GABRIELA (Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community Advanced) study [169]. In both studies, the diversity of microbial exposure in dust samples from children's bedrooms was higher and inversely associated with risk of asthma compared to non-farming communities [170]. ...
Introduction:
Half of all children will experience an episode of wheezing by their sixth birthday and acute episodes of wheezing in preschool children account for the majority of all childhood hospital admissions for wheeze. Recurrent preschool wheezing associates with early loss of lung function and a life-long impact on lung health.
Areas covered:
We reviewed the literature on PubMed from August 2010-2020 focussing on factors associated with wheeze inception and persistence, paying specific attention to mechanistic studies that have investigated the impact of early life exposures in shaping immune responses in children with underlying susceptibility to wheezing. In particular, the role of early allergen sensitization, respiratory infections, and the impact of the environment on shaping the airway microbiome and resulting immune responses are discussed.
Expert opinion:
There is an abundance of associative data showing the role of in utero and postnatal factors influencing wheeze onset and persistence. However, mechanistic and stratified, biomarker-based interventional studies that confirm these associations are now needed if we are to impact the significant healthcare burden resulting from preschool wheezing disorders.
... Early environmental stimuli immunomodulates mucosal responses resulting in changes to lifetime risk of the development of allergic airways disease (AAD) [1][2][3]. Prevention strategies of allergen avoidance have been generally futile [4][5][6][7] however environmental modulation aimed at promoting regulatory immune pathways in the airways have shown promise [3,8]. ...
Background
Trained immunity is the ability of the innate immune system to form immune memory responses to provide support the formation of appropriate adaptive responses. Allergic airways disease (AAD) is a maladapted immune response to allergens, initiated and maintained by the type 2 (T2) inflammatory pathway. It is predicated by the elaboration of cytokines IL-4 and IL-13 and follows activation of the STAT6 transcription factor.
Objective
To investigate the role of trained immunity in mucosal immune responses following neonatal vaccination with the STAT6 inhibitory peptide (STAT6-IP), in preventing the development of ragweed-induced AAD.
Methods
We demonstrate that transfer of CD4 ⁺ T cells or dendritic cells (DC) from STAT6-IP vaccinated wild-type BALB/c mice to naïve mice, that were subsequently chronically exposed to sensitizing doses of ragweed allergen, is sufficient to prevent development of T2 responses in recipients.
Results
Our results demonstrate significant reductions in; airways hyperresponsiveness (AHR); ragweed-specific IgE; pulmonary inflammation; T2 cytokines; and inflammatory gene expressions in recipient mice. Expression of IDO, TGFβ and T regulatory cells were all significantly increased. Anti-TGFβ treatment during the ragweed sensitization phase re-constituted the pro-inflammatory T2 immune response. We show that tolerance can be attained via DC trained in the STAT6-IP-mediated tolerant milieu. This effect is not restricted to a particular allergen and does not require antigen-mediated T cell activation prior to transfer.
Conclusion
Adoptive transfer experiments suggest that STAT6-IP treatment trains dendritic and cells to mediate tolerant immunity to chronic ragweed exposure in the airways. This indicates that early transient STAT6-inhibition constitutes an effective immunomodulatory airways allergy preventative strategy.
... Indeed, multiple studies have explored the indoor aerobiome (airborne microbiome). The PARSIFAL study (Alfven et al., 2006), for example, examined children's mattresses, and the GABRIELA study (Ege et al. 2011) used electrostatic dust collectors placed in the homes to gather aerobiomes. Both studies found greater microbial diversity in the homes of children who lived on farms rather than in cities. ...
Butyrate is an important mediator of human health and disease. The mechanisms of action of Simultaneously, several immune- and inflammatory-mediated diseases are being linked to butyrate are becoming increasingly well-known. Many commensal bacteria that inhabit the human gut can synthesise butyrate, which is then absorbed into the human host. insufficient exposure to beneficial microbes from our environment, including butyrate- producing bacteria. However, the role of outdoor environmental exposure to butyrate- producing bacteria remains poorly understood. Here we review the literature on the human exposure pathways to butyrate-producing bacteria, with a particular focus on outdoor vironmental sources (e.g. associated with plants, plant-based residues, and soil), and the health implications of exposure to them. Emerging evidence suggests that environmental butyrate-producers may help supplement the human gut microbiota and represent an important component of the Biodiversity and Old Friends hypotheses. Improving our understanding of potential sources, precursors, and exposure pathways of environmental butyrate-producers that influence the gut microbiota and butyrate production offers promise to advance multiple disciplines of health and environmental science. We outline research priorities to address knowledge gaps in the outdoor environment-butyrate-health nexus and build knowledge of the potential pathways to help optimise exposure to human-beneficial butyrate-producing bacteria from the outdoor environment during childhood and adulthood.
... Beyond just the examination of nutritional content in organic foods, there is considerable interest in evaluating the impact that organic food has on human health. Current research has begun to show a relationship between organic food consumption and reduced allergic diseases, atopy, CVD, metabolic syndrome, preeclampsia, non-Hodgkin lymphoma, hypospadias and higher sperm concentrations in men (11)(12)(13)(14)(15)(16)(17)(18)(19)(20) . ...
Objective
The association between organic food consumption and biomarkers of inflammation, c-reactive protein (CRP) and cystatin C (CysC), were explored in this cross-sectional analysis of older adults.
Design
Dietary data and organic food consumption was collected in 2013 from a Food Frequency Questionnaire (FFQ). Alternative Mediterranean diet score (A-MedDiet) was calculated as a measure of healthy eating. Biomarkers CRP and CysC were collected in serum or plasma in 2016. We used linear regression models to assess the associations between organic food consumption and CRP and CysC.
Setting
This cross-sectional analysis uses data from the nationally representative, longitudinal panel study of Americans over 50, the Health and Retirement Study (HRS).
Participants
The mean age of the analytic sample (n=3,815) was 64.3(SE 0.3) years with 54.4% being female.
Results
Log CRP and log CysC were inversely associated with consuming organic food after adjusting for potential confounders (CRP: β= -0.096, 95% CI=(-0.159, -0.033)]; CysC: β=-0.033, 95% CI=(-0.051, -0.015)]. Log CRP maintained statistical significance [β=-0.080; 95% CI=(-0.144, -0.016)] after additional adjustments for the A-MedDiet, while log CysC lost statistically significant [β=-0.019; 95% CI=(-0.039, 0.000)]. The association between organic food consumption and log CRP was driven primarily by milk, fruit, vegetables, and cereals while log CysC was primarily driven by milk, eggs, and meat after adjustments for A-MedDiet.
Conclusions
These findings support the hypothesis that organic food consumption is inversely associated with biomarkers of inflammation CRP and CysC, although residual confounding by healthy eating and socioeconomic status cannot be ruled out.
... Early environmental stimuli immunomodulates mucosal responses resulting in changes to lifetime risk of the development of allergic airways disease (AAD) [1][2][3]. Prevention strategies of allergen avoidance have been generally futile [4][5][6][7] however environmental modulation aimed at promoting regulatory immune pathways in the airways have shown promise [3,8]. ...
Background
Allergic airways disease (AAD) is initiated, maintained by the type 2 (T2) inflammatory pathway, and is partially regulated by cytokines IL-4 and IL-13 following activation of the STAT6 transcription factor. Objective
To investigate mucosal immune responses, using neonatal vaccination with the STAT6 inhibitory peptide (STAT6-IP), to prevent the development of ragweed-induced AAD. Methods
We demonstrate that transfer of CD4 ⁺ T cells or dendritic cells (DC) from STAT6-IP vaccinated wild-type BALB/c mice to naïve mice, that were subsequently chronically exposed to sensitizing doses of ragweed allergen, is sufficient to prevent development of T2 responses in recipients. ResultsOur results demonstrate significant reductions in; airways hyperresponsiveness (AHR); ragweed-specific IgE; pulmonary inflammation; T2 cytokines; and inflammatory gene expressions in recipient mice. Expression of IDO, TGFβ and T regulatory cells were all significantly increased. Anti-TGFβ treatment during the ragweed sensitization phase re-constituted the pro-inflammatory T2 immune response. We show that tolerance can be attained via DC or T cells trained in the STAT6-IP-mediated tolerant milieu. This effect is not restricted to a particular allergen and does not require antigen-mediated T cell activation prior to transfer. Conclusion
These data indicate that early transient STAT6-inhibition constitutes an effective immunomodulatory airways allergy preventative strategy.
... In this regard, many researchers have focused on the relationship between allergies and lifestyle and diet as these are somehow changeable factors. Previous surveys have found a close association between increased risk of allergic conditions and a more a uent lifestyle [6][7][8]. Dietary habits may explain at least in part the changes in the prevalence of allergic complications in various regions [9]. ...
Background: There has been an increasing prevalence of allergic disorders globally, and it may be useful to characterize the predisposing and protective factors for the development of allergy. Diet has been identified as one possible environmental factor implicated in the pathogenesis of allergic diseases. The goal of this study was to evaluate the associations between dietary patterns with the presence of allergies in a group of young women in East of Iran
Methods: In total 181 female students enrolled in this study. Presence of allergic diseases including allergic rhinitis (AR), asthma and eczema was confirmed by an expert allergist. Information about dietary intake was collected by using a 65-item validated food frequency questionnaire. Exploratory factor analysis was used to evaluate the relationships among food/nutrition variables.
Result: Multivariate odds ratio of having AR was 2.5 (95% CI:1.1-5.1) for the highest compared to lowest tertile of the Western dietary pattern score. But, no significant relationship was found between the traditional dietary pattern and AR, asthma or eczema.
Conclusion: Our findings indicate a potential role of Western dietary pattern, characterized by being rich in dairy products, snack, nuts and sugar in the development of AR. Since diet is a modifiable impetus, the relationship between AR and Western dietary pattern may has a clinical application, particularly in those who has risk factors for developing AR.
... Previous research on the respiratory health of Swiss children focused on lower respiratory symptoms and farming environment [6][7][8][9][10][11][12]. There are no recent studies and none that includes detailed lung function testing. ...
Respiratory disease is common in children and strongly associated with lifestyle and environmental exposures. Thus, it is important to study the epidemiology locally. LuftiBus in the school (LUIS) was set up to assess the respiratory health of schoolchildren in the canton of Zurich, Switzerland.
LUIS is a cross-sectional population-based study that was carried-out 2013 to 2016. Children aged 6-17 years living in the canton of Zurich were eligible to participate. All schools in the canton were approached and the school head decided whether the school would participate and with which classes. Consenting parents answered a standardized questionnaire at home and assenting children completed a shorter questionnaire by interview at school. Trained technicians measured children’s lung function including spirometry, double tracer gas single-breath washout (DTG-SBW) and fractional exhaled nitric oxide (FeNO). Address histories of participants were geocoded and can be linked with area-based socioeconomic measures and environmental exposures including spatiotemporal air pollution estimates for specific time periods and locations. A subgroup was seen again 12 months later using the same procedures to collect longitudinal data.
The study included 3879 children at baseline and 646 at the one-year follow-up. Median age was 12.7 years; 281 (8%) had wheezed in the past year. At baseline we collected 3466 (89%) parental and 3555 (92%) children’s questionnaires, and 3402 (88%) FeNO, 3478 (90%) spirometry, and 2251 (58%) DTG-SBW measurements. LUIS is a rich resource of health-related data, with information on lung function, environmental exposures and respiratory health on Swiss schoolchildren.
... Alterations within the gut microenvironment are linked to AAS in children (38). Several studies suggest a negative correlation between farming lifestyle during early life and the risk of AAS (39,40) while others identify a specific role for farm-milk FIGURE 1 | Overview of gut microbiota and T cell modulation in allergic asthma. Early-life perturbations, such as broad-spectrum antibiotics, diet, and probiotics, are essential in determining the risk of allergic asthma. ...
Novel methods in immunological research and microbiome evaluation have dramatically changed several paradigms associated with the pathogenesis of allergic asthma (AAS). Ovalbumin and house dust mite-induced AAS in germ-free or specific pathogen-free mice are the two leading experimental platforms that significantly contribute to elucidate the relationship between AAS and gut microbiota. Beyond the exacerbation of T helper (Th) 2 responses, a complex network of immunological interaction driven by gut microbiota could modulate the final effector phase. Regulatory T cells are abundant in gastrointestinal mucosa and have been shown to be pivotal in AAS. The gut microbiota could also influence the activity of other T cell subsets such as Th9, Th17, and populations of effector/memory T lymphocytes. Furthermore, gut microbiota metabolites drive the hematopoietic pattern of dendritic cells and ameliorate lung Th2 immunity in AAS models. The administration of probiotics has shown conflicting results in AAS, and limited evidence is available on the immunological pathways beyond their activity. Moreover, the impact of early-life gut dysbiosis on AAS is well-known both experimentally and clinically, but discrepancies are observed between preclinical and clinical settings. Herein, our aim is to elucidate the most relevant preclinical and clinical scenarios to enlighten the potential role of the gut microbiota in modulating T lymphocytes activity in AAS.
... Other evidence for such an association restricted to more 'old-fashioned' farming comes from the study by Stein et al. [90] in the USA, who compared atopy in children from Amish communities who adhere to strict traditional farm practices, with children from the more modern Hutterite families. Lower risks of type I sensitization and type I allergic disease have however also been found in several other populations of both children and adults who grew up in the last decades in relatively modern farms, as in The Netherlands, Sweden [97][98][99][100][101] and Denmark [11,42,88]. ...
Farmers constitute a large professional group worldwide. In developed countries farms tend to become larger, with a concentration of farm operations. Animal farming has been associated with negative respiratory effects such as work-related asthma and rhinitis. However, being born and raised or working on a farm reduces the risk of atopic asthma and rhinitis later in life. A risk of chronic bronchitis and bronchial obstruction/COPD has been reported in confinement buildings and livestock farmers. This position paper reviews the literature linking exposure information to intensive animal farming and the risk of work-related respiratory diseases and focuses on prevention. Animal farming is associated with exposure to organic dust containing allergens and microbial matter including alive microorganisms and viruses, endotoxins and other factors like irritant gases such as ammonia and disinfectants. These exposures have been identified as specific agents/risk factors of asthma, rhinitis, chronic bronchitis, COPD and reduced FEV1. Published studies on dust and endotoxin exposure in livestock farmers do not show a downward trend in exposure over the last 30 years, suggesting that the workforce in these industries is still overexposed and at risk of developing respiratory disease. In cases of occupational asthma and rhinitis, avoidance of further exposure to causal agents is recommended, but it may not be obtainable in agriculture, mainly due to socio-economic considerations. Hence, there is an urgent need for focus on farming exposure in order to protect farmers and others at work in these and related industries from developing respiratory diseases and allergy.
... Promising in this direction are also clinical studies that are planned in the future. This relates to the scientific data on an experiment, which involved 14,000 children from 5 European countries, aged 5-13, from families with anthroposophical lifestyle, which implies preference for organic (or biodynamic) food; fewer cases of allergies were detected [25]. ...
This paper reports two cake formulations, "Kosmyk" and "Lunik", created by using the principles of the HACCP system, which make it possible to control the safety of devised flour-based products prepared from organic raw materials. The "Kosmyk" cake formulation includes such organic raw materials as rice flour, milled ginger, lemongrass powder, coconut sugar, butter, and sea buckthorn oil, chicken egg mélange, chokeberry jam. The "Lunik" cake formulation includes rice flour in combination with spelt flour, lemongrass powder, coconut sugar, butter, and sea buckthorn oil, chicken egg mélange, organic blackberry jam. The devised products have high organoleptic properties, confirmed by the relevant research. The microbiological and toxicological indicators of the finished products safety have been defined. They do not exceed permissible limits. Since the fat base has been replaced in the developed samples compared to the control formulation, the fatty acid composition of the products has been investigated. The content of saturated fatty acids in both samples decreased by almost twice, whereas the content of monounsaturated fatty acids increased by 1.78 times in the "Kosmyk" sample, and by 1.8 times in the "Lunik" sample. The content of polyunsaturated fatty acids increased by 2.08 times in both samples. The products' fatty acid composition was compared to the composition of "perfect lipid". A block-diagram of production has been constructed, which serves the basis for analysis of hazardous factors. The hazardous factors in the production of flour confectionery products have been analyzed. It has been proposed to use daily safety sheets. The ranking system has been developed to select suppliers.
These results indicate that the use of organic raw materials in the production of cakes makes it possible to expand the existing range of flour-based confectionery products. Adding unconventional oils to the lipid base of a product allows the improvement in the fat-acid composition. The obtained results could be applied by the confectionery industry to manufacture new products and to implement a food safety management system
In 1989, a short paper entitled “Hay fever, hygiene and household size” observed that British children from larger families were less likely to develop hay fever and suggested that this could be because early exposure to infection prevents allergy. This sibship size association for hay fever, since replicated many times in Britain and other affluent countries and confirmed by objective measures of atopy, prompted what has come to be known as the “hygiene hypothesis for allergy”, although that term was not specifically used in the 1989 paper. The present paper reviews the historical roots of the “hygiene hypothesis” and charts its development over more than 30 years. Initial scepticism among immunologists turned to enthusiasm in the mid-1990s as the Th1/Th2 paradigm for allergic sensitisation emerged from animal experiments and the concept of “immunological old friends” became popular from the early 2000s. From the late 1990s, observations of reduced allergy risk among children of anthroposophic families and those brought up on farms suggested that the sibship size effects formed part of a broader range of “hygiene-related” determinants of allergy. Children from large families with farming exposure have approximately sixfold reduction in prevalence of hay fever, indicating the potential strength and epidemiological importance of these environmental determinants. During the 21st century, a wide range of specific microbial, environmental and lifestyle factors have been investigated as possible underlying mechanisms, but sadly none have emerged as robust explanations for the family size and farming effects. Thus, while the “hygiene hypothesis” led to a fundamental reappraisal of our relationship with our microbial environment and to the concept that early exposure, rather than avoidance, is beneficial for developing a healthy immune system, the underlying mechanism for variations in allergy prevalence with family size remains, in Churchillian terms, “a riddle wrapped in a mystery inside an enigma”.
This chapter discusses the research on the influence of the environment of a livestock farm in the protection against the occurrence of allergic diseases during the life of an individual. It was the observation of an unprecedented increase in allergic diseases in the European, American and Japanese populations after Second World War that precipitated the implementation of research in these areas. Since the 1990s, a large number of cross‐sectional epidemiological studies have supplemented the initial observations of the 1980s. The combination of these epidemiological results gave rise to the explanatory hypothesis of “hygiene”, capable of accounting for the observations by resituating them in the immunological concepts of the time. As in the population‐based studies, it was the observation of protection by raw milk consumption that was also the most consistent finding in the analyses from the Protection Against Allergy: Study in Rural Environments cohort.
Background:
Asthma is one of the most common chronic diseases in childhood and the prevalence has been increasing over the past few decades. One of the most consistent epidemiological findings is that children living in a farming or rural environment are protected from development of asthma and allergies, but the protective factors in rural China are not clear.
Methods:
A community-based, cross-sectional epidemiological study was performed in a total of 17,587 children aged 5-8 years, 3,435 from Hong Kong (urban) and 14,152 from Conghua (rural county in southern China). Asthma and allergic symptoms as well as environmental exposures were ascertained by using a standardized and validated questionnaire.
Results:
The prevalence of current wheeze was significantly lower in rural Conghua than that of urban Hong Kong (1.7% vs. 7.7%, P < 0.001). A lower rate of asthma ever was also reported in rural children compared with their urban counterparts (2.5% vs. 5.3%, P < 0.001). After adjusting for confounding factors, exposure to agricultural farming (adjusted odds ratio 0.74, 95% confidence interval: 0.56-0.97) and poultry (0.75, 0.59-0.96) were the most important factors associated with the asthma-protective effect in the rural area. Further propensity score adjusted analysis indicated that such protection conferred by living in the rural environment was mainly attributable to poultry exposure.
Conclusions:
We confirmed that the prevalence of asthma and atopic disorders was significantly lower in rural children when compared with their urban peers. Exposure to poultry and agricultural farming are the most important factors associated with asthma protection in the rural area.
Background:
Changes in immune cell composition during the immunological window within the first years after birth are not fully understood, especially the effect that different lifestyles might have on immune cell functionality.
Methods:
Peripheral blood mononuclear cells from mothers and their children at birth and at two and five years were analyzed by mass cytometry. Immune cell composition and functionality was analyzed according to family lifestyle (anthroposophic and non-anthroposophic).
Results:
We found no significant differences in the proportions of major immune lineages between anthroposophic and non-anthroposophic children at each timepoint, but there were clear changes over time in the proportions of mononuclear leukocytes, especially in B cells and T lymphocytes. Phenotypic distances between cord blood and maternal blood were high at birth but decreased sharply the first two years, indicating strong phenotypic convergence with maternal cells. We found that children exhibited similar stimulation responses at birth, but subsequently segregated into two discrete functional trajectories. Trajectory 1 was associated with a decrease in tumor necrosis factor alpha (TNFa) production by CD4+ T- and NK-cells, while Trajectory 2 depicted an increase in the production of IL-2 and interferon gamma (INFg) by T-cells. In both trajectories there was an increase in IL-17A production by T-cells resulting in prominent differences at five years of age.
Conclusions:
This exploratory study suggest that leukocyte frequencies and cell phenotypes change with age in the same way across all children, while functional development follow one of two discrete trajectories that largely segregate by family lifestyle, supporting the hypothesis that early environmental exposures imprint immune cell function which may contribute to IgE sensitization. Our results also support that the first two years are critical for the environmental exposures to imprint the immune cells. Further studies with larger sample sizes are required to validate our findings.
Rationale: In murine models, microbial exposures induce protection from experimental allergic asthma through innate immunity. Objectives: Our aim was to assess the association of early life innate immunity with the development of asthma in children at risk. Methods: In the PASTURE farm birth cohort, innate T-helper cell type 2 (Th2), Th1, and Th17 cytokine expression at age 1 year was measured after stimulation of peripheral blood mononuclear cells with LPS in n = 445 children. Children at risk of asthma were defined based on single-nucleotide polymorphisms at the 17q21 asthma gene locus. Specifically, we used the SNP rs7216389 in the GSDMB gene. Wheeze in the first year of life was assessed by weekly diaries and asthma by questionnaire at age 6 years. Measurements and Main Results: Not all cytokines were detectable in all children after LPS stimulation. When classifying detectability of cytokines by latent class analysis, carrying the 17q21 risk allele rs7216389 was associated with risk of wheeze only in the class with the lowest level of LPS-induced activation: odds ratio (OR), 1.89; 95% confidence interval [CI], 1.13-3.16; P = 0.015. In contrast, in children with high cytokine activation after LPS stimulation, no association of the 17q21 risk allele with wheeze (OR, 0.63; 95% CI, 0.29-1.40; P = 0.258, P = 0.034 for interaction) or school-age asthma was observed. In these children, consumption of unprocessed cow's milk was associated with higher cytokine activation (OR, 3.37; 95% CI, 1.56-7.30; P = 0.002), which was in part mediated by the gut microbiome. Conclusions: These findings suggest that within the 17q21 genotype, asthma risk can be mitigated by activated immune responses after innate stimulation, which is partly mediated by a gut-immune axis.
The prevalence of allergic disorders has been increasing globally, and it may be useful to identify the modifiable factors associated with it. Diet has been identified as one possible lifestyle factor implicated in the pathogenesis of allergic diseases. The goal of this study was to evaluate the associations between dietary patterns and the presence of allergies in a group of young women in eastern Iran. In all, 181 female students were enrolled. Screening for presence of allergic diseases, including allergic rhinitis (AR), asthma and eczema, was performed by an expert allergist. Information about dietary intake was collected using a validated 65-item food frequency questionnaire. Exploratory factor analysis was used to evaluate the relationships between food/nutrition variables. Serum immunoglobulin (Ig)E levels were significantly higher in the group in the third tertile (highest adherence) for a Western dietary pattern compared to the group in the first tertile (lowest adherence). The multivariate odds ratio for presence of allergic rhinitis (AR) was 2.5 (95% CI:1.1-5.1) for the highest compared to lowest tertile of the Western dietary pattern score. However, no significant relationship was found between a traditional dietary pattern and AR, asthma or eczema. Our findings indicate a potential role in the development of AR of the Western dietary pattern, which is characterized by high intake of dairy products, snacks, nuts and sugar. Since diet is a modifiable factor, the relationship between AR and a Western dietary pattern may have clinical implications, particularly in subjects with other risk factors for developing AR.
Allergic diseases are an increasing global burden. Epidemiological and in vivo studies showed that farming environments could protect from allergic asthma. Studies explaining this protective effect mainly focused on the influence of chemical compounds in the molecular size range of proteins and endotoxins. Our study aimed at deciphering the possible role of small-sized semi-volatile organic compounds (SVOCs) of farming aerosols in immunomodulation processes. Bronchial epithelial BEAS-2B cells were exposed to aerosol extracts of particulate matter (PM2.5) from farming environments. These cell exposures revealed a decisive effect of the smaller sized fraction (< 3 kDa) compared to extracts including the larger sized fraction. We demonstrated that smaller compounds can induce regulations of inflammatory and allergy-related genes including interleukin-8, xanthine dehydrogenase and toll-like receptor 2 (TLR2). Additionally, we performed a comprehensive chemical investigation of two typical farming aerosols (cow vs. sheep) by applying comprehensive gas chromatography coupled to time-of-flight mass spectrometry. We were able to identify several SVOCs characteristic for the protective cow sheds environment including four key components. Cell exposure with the two farming extracts showed a distinct regulation of the E3 ubiquitin ligase PELI2 gene and TLR2 by cow shed extracts. Finally, the regulation of TLR2 corresponded to the regulation that was observed after exposing cells to an artificial mixture of the four key components identified in the cow sheds. In summary, we were able to demonstrate the importance of smaller particle-bound SVOCs found in farming environments concerning their possible contribution to a protective farm effect.
Organic farming is an environmentally, economically and socially accepted way to produce food. This review scrutinizes various facets of the practice including its impact on the environment, international markets, and local as well as global food security. First-hand knowledge throughout India and the world was evaluated the various strategies and policies implemented for organic agriculture in India. Scenarios depicted here represent millions of people from all social and economic backgrounds who have embraced this agrarian method ensuring the integrity of food. Since organic farming depends on animal manures, off-farm organic wastes, crop residues, green manures, and bio-fertilizers, the question arises whether the availability of these organic feed materials is sufficient to support widespread organic farming in India. In total, these sources could supply 7.04 Mt. of primary nutrients in India, while in the long-term, organic farming could contribute to food security by harmonizing population growth, food grain production, fertilizer consumption, and prevent or minimize soil nutrient depletion. Municipal solid waste compost and sewage water are being increasingly employed in organic agriculture and very large amounts of organic residues and pollutants are added to the soil. Given this, the prospects of organic agriculture to help solve environmental problems need to be researched in more detail. Soil C (carbon) sequestration by municipal solid waste compost and sewage water may to some extent stop environmental degradation. Primarily, organic farming could boost the quality of food by enhancing protein, vitamins, minerals, etc. Soil health and ecological functions such as biomass production, biodiversity maintenance, environmental protection, etc., which occur in organic farming could also be maintained or improved. In this way, it is possible for climatic aberrations could be mitigated or alleviated. However, policies should be developed for proper utilization of bio-waste, integrated farming approaches with organics, prioritizing areas and different kinds of organic farming, better pest management involving bio-pesticides, strengthening the domestic market for organic produce, farmer-to-farmer communication, etc. Our assessment found that organic farming has huge potential for contributing to food security, risk mitigation, etc., in India. Organic farming could also address many of the sustainable development goals directly, namely 3, 5, 6, 11, 12, 13, 14, 15 and 16. However, future research should address areas like: (a) C sequestration and critical C input for organic farming; (b) dynamics, biology and biochemistry of nutrient cycles; (c) impact of the exposure of organic farming to contaminants; and (d) producing higher quality food crops.
Ziel: Evaluierung einer Lutschtablette zur Mikronährstoff-Supplementierung basierend auf dem Bauernhof-Effekt, bei Patienten mit Hausstaubmilben(HDM)- assoziierter allergischer Rhinokonjunktivitis (ARC) in einer standardisierten Allergen-Expositionskammer (AEC). Methoden: Vor (V1) und nach (V3) täglicher Supplementierung mit holo-BLG (BLG, β-Lactoglobulin) über einen Zeitraum von drei Monaten wurden Patienten mit HDM-Allergie für jeweils zwei Stunden in einer AEC mit einem HDM-Extrakt provoziert. Die durch die HDM-Exposition ausgelösten nasalen, konjunktivalen, bronchialen und sonstigen Symptome wurden im Abstand von jeweils zehn Minuten durch die Patienten bewertet. Allgemeines Wohlbefinden, "peak nasal inspiratory flow" (PNIF) sowie Lungenfunktion wurden alle 30 Minuten evaluiert. Primärer Endpunkt der Studie war die Änderung der Summe der nasalen Symptome (TNSS, totaler nasaler Symptomscore) am Ende der zweiten Exposition (V3) im Vergleich zur ersten (V1). Ein wichtiger sekundärer Endpunkt war die vergleichende Analyse des zeitlichen Verlaufs aller Symptomscores während V1 zu V3 mittels eines gemischten linearen Modells. Ergebnisse: 32 Patienten wurden in die Analyse eingeschlossen. Es wurde eine signifikante Verbesserung von 60 % (p = 0,0034) im primären Endpunkt-TNSS (V1: 2,5 [IQR: 1-4]; V3: 1,0 [IQR: 1-3]) gemessen sowie eine 40 %ige Verbesserung im totalen Symptomscore (TSS; V1: 5,0 [IQR: 3-9]; V3: 3,0 [IQR: 2-4]; Wilcoxon-Test: CI: 1,5-4,0; p < 0,0003). Sowohl der zeitliche Verlauf aller Symptomscores als auch das persönliche Wohlbefinden verbesserten sich in einem klinisch relevanten Ausmaß, beispielsweise sichtbar durch den geringeren Anstieg der Symptome während der finalen HDM-Exposition. Es gab keine wesentlichen Änderungen für PNIF und Lungenfunktion. Die Sicherheit und Verträglichkeit der Lutschtablette wurden als hervorragend eingestuft. Schlussfolgerung: Die Wirkung von holo-BLG, das durch gezielte Mikronährstoff-Supplementierung zur Immunresilienz bei Immunzellen führt, bietet einen neuen Ansatz zur Eindämmung der aktuellen Allergie-Epidemie. Zitierweise: Bergmann K-C, Graessel A, Raab J, Banghard W, Krause L, Becker S, Kugler S, Zuberbier T, Ott VB, Kramer MF, Roth-Walter F, Jensen-Jarolim E, Guethoff S. Targeted micronutrition via holo-BLG based on the farm effect in house dust mite allergic rhinoconjunctivitis patients - first evaluation in a standardized allergen exposure chamber. Allergo J Int 2021;30:141-9 https://doi.org/10.1007/s40629-021-00163-9
Background and Objectives
Childhood atopy is a complex condition with both a genetic and an environmental component. This systematic review will explore the current understanding of the importance of early life exposures to a farm in the development of atopy measured by objective markers of skin prick testing, and specific IgE measurements in school age children.
Methods
A systematic review was performed.
Results
Among 7285 references identified, 14 studies met the inclusion criteria (13 cross-sectional studies and 1 case-control study). The results were fairly consistent in that early farm-related exposures can protect children from becoming atopic at school age. In general, there was heterogeneity in the assessment of outcomes and exposures.
Conclusions
Early-life farm exposures are associated with a protective effect on childhood atopy as assessed by objective markers. Future work should focus on understanding specific farm exposures that may important in these associations between atopy and farm exposures in children.
Poxviruses employ many strategies to evade and neutralize the host immune response. In this study, we have identified two
vaccinia virus ORFs, termed A46R and A52R, that share amino acid sequence similarity with the Toll/IL-1 receptor (TIR) domain,
a motif that defines the IL-1/Toll-like receptor (TLR) superfamily of receptors, which have a key role in innate immunity
and inflammation. When expressed in mammalian cells, the protein products of both ORFs were shown to interfere specifically
with IL-1 signal transduction. A46R partially inhibited IL-1-mediated activation of the transcription factor NFκB, and A52R
potently blocked both IL-1- and TLR4-mediated NFκB activation. MyD88 is a TIR domain-containing adapter molecule known to
have a central role in both IL-1 and TLR4 signaling. A52R mimicked the dominant-negative effect of a truncated version of
MyD88 on IL-1, TLR4, and IL-18 signaling but had no effect on MyD88-independent signaling pathways. Therefore, A46R and A52R
are likely to represent a mechanism used by vaccinia virus of suppressing TIR domain-dependent intracellular signaling.
The aetiology of asthma and allergic disease remains poorly understood, despite considerable research. The International Study of Asthma and Allergies in Childhood (ISAAC), was founded to maximize the value of epidemiological research into asthma and allergic disease, by establishing a standardized methodology and facilitating international collaboration. Its specific aims are: 1) to describe the prevalence and severity of asthma, rhinitis and eczema in children living in different centres, and to make comparisons within and between countries; 2) to obtain baseline measures for assessment of future trends in the prevalence and severity of these diseases; and 3) to provide a framework for further aetiological research into genetic, lifestyle, environmental, and medical care factors affecting these diseases. The ISAAC design comprises three phases. Phase 1 uses core questionnaires designed to assess the prevalence and severity of asthma and allergic disease in defined populations. Phase 2 will investigate possible aetiological factors, particularly those suggested by the findings of Phase 1. Phase 3 will be a repetition of Phase 1 to assess trends in prevalence.
Mutations of the gene Lps selectively impede lipopolysaccharide (LPS) signal transduction in C3H/HeJ and C57BL/10ScCr mice, rendering them resistant
to endotoxin yet highly susceptible to Gram-negative infection. The codominantLps
d allele of C3H/HeJ mice was shown to correspond to a missense mutation in the third exon of the Toll-like receptor-4 gene
(Tlr4), predicted to replace proline with histidine at position 712 of the polypeptide chain. C57BL/10ScCr mice are homozygous
for a null mutation of Tlr4. Thus, the mammalian Tlr4 protein has been adapted primarily to subserve the recognition of LPS and presumably transduces
the LPS signal across the plasma membrane. Destructive mutations of Tlr4 predispose to the development of Gram-negative sepsis, leaving most aspects of immune function intact.
Unmethylated CpG motifs are prevalent in bacterial but not vertebrate genomic DNAs. Oligodeoxynucleotides (ODN) containing CpG motifs activate host defense mechanisms leading to innate and acquired immune responses. The recognition of CpG motifs requires Toll-like receptor (TLR) 9, which triggers alterations in cellular redox balance and the induction of cell signaling pathways including the mitogen activated protein kinases (MAPKs) and NF kappa B. Cells that express TLR-9, which include plasmacytoid dendritic cells (PDCs) and B cells, produce Th1-like proinflammatory cytokines, interferons, and chemokines. Certain CpG motifs (CpG-A) are especially potent at activating NK cells and inducing IFN-alpha production by PDCs, while other motifs (CpG-B) are especially potent B cell activators. CpG-induced activation of innate immunity protects against lethal challenge with a wide variety of pathogens, and has therapeutic activity in murine models of cancer and allergy. CpG ODN also enhance the development of acquired immune responses for prophylactic and therapeutic vaccination.
In early life, the innate immune system can recognize both viable and nonviable parts of microorganisms. Immune activation may direct the immune response, thus conferring tolerance to allergens such as animal dander or tree and grass pollen.
Parents of children who were 6 to 13 years of age and were living in rural areas of Germany, Austria, or Switzerland where there were both farming and nonfarming households completed a standardized questionnaire on asthma and hay fever. Blood samples were obtained from the children and tested for atopic sensitization; peripheral-blood leukocytes were also harvested from the samples for testing. The levels of endotoxin in the bedding used by these children were examined in relation to clinical findings and to the cytokine-production profiles of peripheral-blood leukocytes that had been stimulated with lipopolysaccharide and staphylococcal enterotoxin B. Complete data were available for 812 children.
Endotoxin levels in samples of dust from the child's mattress were inversely related to the occurrence of hay fever, atopic asthma, and atopic sensitization. Nonatopic wheeze was not significantly associated with the endotoxin level. Cytokine production by leukocytes (production of tumor necrosis factor alpha, interferon-gamma, interleukin-10, and interleukin-12) was inversely related to the endotoxin level in the bedding, indicating a marked down-regulation of immune responses in exposed children.
A subject's environmental exposure to endotoxin may have a crucial role in the development of tolerance to ubiquitous allergens found in natural environments.
Human cytomegalovirus (CMV) is a ubiquitous opportunistic pathogen that causes significant morbidity and mortality in immuncompromised
people. An understanding of how CMV induces and circumvents host immunity is of critical importance in efforts to design effective
therapeutics. It was recently discovered that mere cell contact by CMV particles leads to profound modulation of cellular
gene expression, including induction of inflammatory cytokines and interferon-stimulated genes characteristic of innate immune
detection. These findings suggest that a membrane receptor recognizes a CMV envelope protein(s), leading to innate immune
activation. Here, we show that the pattern recognition receptors Toll-like receptor 2 (TLR2) and CD14 recognize CMV virions
and trigger inflammatory cytokine production. Induction of inflammatory cytokines is mediated via TLR2-dependent activation
of NF-κB. Since many of the pathological processes associated with CMV disease are facilitated or directly mediated by inflammatory
cytokines, identification of the host membrane detection machinery may ultimately lead to improved therapeutics.
Plasmacytoid dendritic cells (pDCs) have been identified as a potent secretor of the type I interferons (IFNs) in response to CpG as well as several viruses. In this study, we examined the molecular mechanism of virus recognition by pDCs. First, we demonstrated that the CD11c+Gr-1intB220+ pDCs from mouse bone marrow secreted high levels of IFN-alpha in response to either live or UV-inactivated Herpes simplex virus-2 (HSV-2). Next, we identified that IFN-alpha secretion by pDCs required the expression of the adaptor molecule MyD88, suggesting the involvement of a Toll-like receptor (TLR) in HSV-2 recognition. To test whether a TLR mediates HSV-2-induced IFN-alpha secretion from pDCs, various knockout mice were examined. These experiments revealed a clear requirement for TLR9 in this process. Further, we demonstrated that purified HSV-2 DNA can trigger IFN-alpha secretion from pDCs and that inhibitory CpG oligonucleotide treatment diminished HSV-induced IFN-alpha secretion by pDCs in a dose-dependent manner. The recognition of HSV-2 by TLR9 was mediated through an endocytic pathway that was inhibited by chloroquine or bafilomycin A1. The strict requirement for TLR9 in IFN-alpha secretion was further confirmed by the inoculation of HSV-2 in vivo. Therefore, these results demonstrate a novel mechanism whereby the genomic DNA of a virus can engage TLR9 and result in the secretion of IFN-alpha by pDCs.
Studies have suggested that children living close to busy roads may have impaired respiratory health. This study was designed to test the hypothesis that exposure to exhaust from heavy traffic in particular is related to childhood respiratory health. Children attending 24 schools located within 400 m from busy motorways were investigated. The motorways carried between 5,190 and 22,326 trucks per weekday and between 30,399 and 155,656 cars per day. Locations were chosen so that the correlation between truck and car traffic counts was low. Air pollution measurements were performed at the schools for 1 year. Respiratory symptoms were collected by parent-completed questionnaire. Sensitization to common allergens was measured by serum immunoglobulin E and skin prick tests. Bronchial hyperresponsiveness (BHR) was measured with a hypertonic saline challenge. Respiratory symptoms were increased near motorways with high truck but not high car traffic counts. They were also related to air pollutants that increased near motorways with high truck traffic counts. Lung function and BHR were not related to pollution. Sensitization to pollen increased in relation to truck but not car traffic counts. The relation between symptoms and measures of exposure to (truck) traffic-related air pollution were almost entirely restricted to children with BHR and/or sensitization to common allergens, indicating that these are a sensitive subgroup among all children for these effects.
Recognition of pathogens by Toll-like receptors (TLRs) triggers innate immune responses through signaling pathways mediated by Toll-interleukin 1 receptor (TIR) domain-containing adaptors such as MyD88, TIRAP and TRIF. MyD88 is a common adaptor that is essential for proinflammatory cytokine production, whereas TRIF mediates the MyD88-independent pathway from TLR3 and TLR4. Here we have identified a fourth TIR domain-containing adaptor, TRIF-related adaptor molecule (TRAM), and analyzed its physiological function by gene targeting. TRAM-deficient mice showed defects in cytokine production in response to the TLR4 ligand, but not to other TLR ligands. TLR4- but not TLR3-mediated MyD88-independent interferon-beta production and activation of signaling cascades were abolished in TRAM-deficient cells. Thus, TRAM provides specificity for the MyD88-independent component of TLR4 signaling.
The prevalence of symptoms of asthma, allergic rhinitis, and atopic eczema in children in the United Kingdom ranks among the highest in the world.1 The evidence from most repeat surveys is that prevalence has increased over the past three decades,2 but the most recent of these studies observed that from 1991 to 1998 the increase was confined to milder symptoms of asthma.3 Since the early 1990s the incidence of asthma episodes presenting to general practitioners, and of hospital admissions, has fallen substantially.2
Prevalence rates of childhood asthma and allergy have been on the increase for several decades. The present study investigated whether this trend continued during the 1990s in adolescents living in Switzerland. Between 1992 and 2000, the change in prevalence of specific immunoglobulin E to aeroallergens, asthma symptoms and hay fever symptoms assessed by parents' and students' answers to the International Study of Asthma and Allergies in Childhood questions was investigated using three cross-sectional surveys. In total 1,324 (74.9%), 1,668 (80.6%) and 1,250 (73.9%) adolescents participated. Prevalence rates of asthma and current asthmatic symptoms remained constant, irrespective of whether the assessment was based on parental questionnaires or the student's self-completed written or video questionnaires (students' report of current wheeze 8.8, 7.3, and 8.3%). Similarly, no further increase was observed for reported hay fever rates and allergic sensitisation rates (positive multiscreen allergy test, SX1-test: 34.6, 38.9, and 35.6%, respectively). Although time trends in the occurrence of a series of known risk factors were recorded, none of these factors had a significant impact on asthma and allergy prevalence over time. No further increase in asthma and allergy rates occurred during the 1990s in adolescents living in Switzerland. However, to adequately assess the trend a longer period of observation is needed.
TANK-binding kinase-1 (TBK1) and the inducible IkappaB kinase (IKK-i) have been shown recently to activate interferon (IFN) regulatory factor-3 (IRF3), the primary transcription factor regulating induction of type I IFNs. Here, we have compared the role and specificity of TBK1 in the type I IFN response to lipopolysaccharide (LPS), polyI:C, and viral challenge by examining IRF3 nuclear translocation, signal transducer and activator of transcription 1 phosphorylation, and induction of IFN-regulated genes. The LPS and polyI:C-induced IFN responses were abolished and delayed, respectively, in macrophages from mice with a targeted disruption of the TBK1 gene. When challenged with Sendai virus, the IFN response was normal in TBK1(-/-) macrophages, but defective in TBK1(-/-) embryonic fibroblasts. Although both TBK1 and IKK-i are expressed in macrophages, only TBK1 but not IKK-i was detected in embryonic fibroblasts by Northern blotting analysis. Furthermore, the IFN response in TBK1(-/-) embryonic fibroblasts can be restored by reconstitution with wild-type IKK-i but not a mutant IKK-i lacking kinase activity. Thus, our studies suggest that TBK1 plays an important role in the Toll-like receptor-mediated IFN response and is redundant with IKK-i in the response of certain cell types to viral infection.
We investigated the Toll-like receptor 2 (TLR2) Arg677Trp polymorphism, associated with lepromatous leprosy in the Korean population and shown to abrogate TLR2-mediated signalling in response to mycobacterial ligands, in 286 Indian leprosy patients and 183 ethnically matched controls. The case-control comparison also involved investigation of possible variation(s) in the promoter region of the TLR2 gene. Genotyping results after direct PCR sequencing showed that the TLR2 Arg677Trp polymorphism associated with lepromatous leprosy in the Korean population is not a true polymorphism of the TLR2 gene and has resulted from the variation present in the 93% homologous duplicated region of TLR2 exon 3 present approximately 23 kb upstream.
The complete sequences of Takifugu Toll-like receptor (TLR) loci and gene predictions from many draft genomes enable comprehensive molecular phylogenetic analysis. Strong selective pressure for recognition of and response to pathogen-associated molecular patterns has maintained a largely unchanging TLR recognition in all vertebrates. There are six major families of vertebrate TLRs. This repertoire is distinct from that of invertebrates. TLRs within a family recognize a general class of pathogen-associated molecular patterns. Most vertebrates have exactly one gene ortholog for each TLR family. The family including TLR1 has more species-specific adaptations than other families. A major family including TLR11 is represented in humans only by a pseudogene. Coincidental evolution plays a minor role in TLR evolution. The sequencing phase of this study produced finished genomic sequences for the 12 Takifugu rubripes TLRs. In addition, we have produced >70 gene models, including sequences from the opossum, chicken, frog, dog, sea urchin, and sea squirt.
The response of drosophila to bacterial and fungal infections involves two signaling pathways, Toll and Imd, which both activate members of the transcription factor NF-kappaB family. Here we have studied the global transcriptional response of flies to infection with drosophila C virus. Viral infection induced a set of genes distinct from those regulated by the Toll or Imd pathways and triggered a signal transducer and activator of transcription (STAT) DNA-binding activity. Genetic experiments showed that the Jak kinase Hopscotch was involved in the control of the viral load in infected flies and was required but not sufficient for the induction of some virus-regulated genes. Our results indicate that in addition to Toll and Imd, a third, evolutionary conserved innate immunity pathway functions in drosophila and counters viral infection.
The cellular protein retinoic acid-inducible gene I (RIG-I) senses intracellular viral infection and triggers a signal for innate antiviral responses including the production of type I IFN. RIG-I contains a domain that belongs to a DExD/H-box helicase family and exhibits an N-terminal caspase recruitment domain (CARD) homology. There are three genes encoding RIG-I-related proteins in human and mouse genomes. Melanoma differentiation associated gene 5 (MDA5), which consists of CARD and a helicase domain, functions as a positive regulator, similarly to RIG-I. Both proteins sense viral RNA with a helicase domain and transmit a signal downstream by CARD; thus, these proteins share overlapping functions. Another protein, LGP2, lacks the CARD homology and functions as a negative regulator by interfering with the recognition of viral RNA by RIG-I and MDA5. The nonstructural protein 3/4A protein of hepatitis C virus blocks the signaling by RIG-I and MDA5; however, the V protein of the Sendai virus selectively abrogates the MDA5 function. These results highlight ingenious mechanisms for initiating antiviral innate immune responses and the action of virus-encoded inhibitors.
Development of the acute and chronic inflammatory responses known as gout and pseudogout are associated with the deposition of monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals, respectively, in joints and periarticular tissues. Although MSU crystals were first identified as the aetiological agent of gout in the eighteenth century and more recently as a 'danger signal' released from dying cells, little is known about the molecular mechanisms underlying MSU- or CPPD-induced inflammation. Here we show that MSU and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin) inflammasome, resulting in the production of active interleukin (IL)-1beta and IL-18. Macrophages from mice deficient in various components of the inflammasome such as caspase-1, ASC and NALP3 are defective in crystal-induced IL-1beta activation. Moreover, an impaired neutrophil influx is found in an in vivo model of crystal-induced peritonitis in inflammasome-deficient mice or mice deficient in the IL-1beta receptor (IL-1R). These findings provide insight into the molecular processes underlying the inflammatory conditions of gout and pseudogout, and further support a pivotal role of the inflammasome in several autoinflammatory diseases.
The prevalence of atopic diseases is on the rise. Traditional lifestyles may be associated with a reduced risk of atopy.
To test the hypothesis that children living on a farm have lower prevalences of atopic diseases. To identify differences in living conditions between farmers and other families which are associated with the development of atopic conditions.
Cross-sectional survey among children entering school (aged 5-7 years). A written questionnaire including the ISAAC core questions and asking for exposures on a farm and elsewhere was administered to the parents. Setting: School health entry examination in two Bavarian districts with extensive farming activity. Subjects: 10 163 children.
The prevalence of doctor's diagnoses and symptoms of hay fever, asthma and eczema as assessed by parental report.
Farmers' children had lower prevalences of hay fever (adjusted odds ratio = 0. 52, 95% CI 0.28-0.99), asthma (0.65, 0.39-1.09), and wheeze (0.55, 0. 36-0.86) than their peers not living in an agricultural environment. The reduction in risk was stronger for children whose families were running the farm on a full-time basis as compared with families with part-time farming activity. Among farmers' children increasing exposure to livestock was related to a decreasing prevalence of atopic diseases (aOR = 0.41, 95% CI 0.23-0.74).
Factors related to environmental influences on a farm such as increased exposure to bacterial compounds in stables where livestock is kept prevent the development of allergic disorders in children.
IntroductionLower prevalence rates of allergic diseases in rural as compared with urban populations have been interpreted as indicating an effect of air pollution. However, little is known about other factors of the rural environment which may determine the development of atopic sensitization and related diseases.Objective
The authors tested the hypothesis that children growing up on a farm were less likely to be sensitized to common aerollergens and to suffer from allergic diseases than children living in the same villages but in nonfarming families.Materials and methodsThree age groups of schoolchildren (6–7 years, 9–11 years, 13–15 years) living in three rural communities were included in the analyses. An exhaustive questionnaire was filled in by 1620 (86.0%) parents. A blood sample was provided by 404 (69.3%) of the 13–15 year olds to determine specific IgE antibodies against six common aeroallergens.ResultsFarming as parental occupation was reported for 307 children (19.0%). After adjustment for potential covariates such as family history of asthma and allergies, parental education, number of siblings, maternal smoking, pet ownership, indoor humidity and heating fuels, farming as parental occupation was significantly associated with lower rates of sneezing attacks during pollen season (adjusted OR 0.34, 95% CI 0.12–0.89) and atopic sensitization (adjusted OR 0.31, 95% CI 0.13–0.73) whereas the association with wheeze (adjusted OR 0.77 95% CI 0.38–1.58) and itchy skin rash (adjusted OR 0.86, 95% CI 0.49–1.50) was not statistically significant. The risk of atopic sensitization was lower in children from full-time farmers (adjusted OR 0.24, 95% CI 0.09–0.66) than from part-time farmers (adjusted OR 0.54, 95% CI 0.15–1.96).Conclusion
Factors directly or indirectly related to farming as parental occupation decrease the risk of children becoming atopic and developing symptoms of allergic rhintis.
To estimate changes in the prevalence of reported symptoms of respiratory disease and reported diagnoses of asthma and bronchitis in primary school children in England between 1973 and 1986.
Mixed longitudinal survey.
Representative sample of English primary schools in 22 areas.
15,000 Boys and 14,156 girls each studied at least once between 1973 and 1986.
Whether, according to the parent or guardian, the child had wheezed, wheezed on most days or nights, or had attacks of bronchitis or asthma in the past year.
Within age groups trends in successive annual cohorts showed an increasing prevalence of asthma for each annual birth cohort (boys, 6.9%, p less than 0.001; girls, 12.8%, p less than 0.001) and of wheeze on most days or nights (boys, 4.3% per cohort, p less than 0.001; girls, 6.1% per cohort, p less than 0.001) and a falling prevalence of bronchitis (boys, -4.7% per cohort, p less than 0.001; girls, -5.8% per cohort, p less than 0.001). There was a smaller increase in the prevalence of wheeze whether or not it occurred on most days or nights, and this increase was significant only among the girls (boys, 1.0% per cohort, p greater than 0.05; girls, 1.7% per cohort, p less than 0.05). Although the rate of increase of "asthma" was greater than the rate of decrease in "bronchitis," the baseline prevalence of asthma was much lower than that of bronchitis, and the total proportion of children with either diagnosis declined slightly over the whole period. The main change was an increase in the proportion of children whose parents stated that they had persistent wheeze and yet did not have a report of either "asthma" or "bronchitis."
These results suggest that there has been a true increase in morbidity that is not simply due to changes in diagnostic fashion. The increase is large enough to explain much if not all of the increase in admission to hospital and mortality, and it underlines the importance of an understanding of the aetiology of asthma in tackling the causes of the recent increase.
Lower prevalence rates of allergic diseases in rural as compared with urban populations have been interpreted as indicating an effect of air pollution. However, little is known about other factors of the rural environment which may determine the development of atopic sensitization and related diseases.
The authors tested the hypothesis that children growing up on a farm were less likely to be sensitized to common aerollergens and to suffer from aller